Phase II Multicentric Randomized Trial, Evaluating the Best Protocol of Chemotherapy, Associated With Targeted Therapy According to the Tumor KRAS Status, in Metastatic Colorectal Cancer (CCRM) Patients With Initially Non-resectable Hepatic Metastases
- Histologically proven colorectal adenocarcinoma,
- Primary tumor of the colon or rectum, resectable or resected at least 3 weeks before
randomization or 4 weeks before the beginning of the study treatment,
- Metastatic disease with synchronous or metachronous (> 3 months after diagnosis of
the primary tumor) hepatic metastasis,
- Non-resectable (with respect to curative intent) hepatic metastasis at presentation.
This criterion must be validated by both a surgeon and a radiologist during the RCP
(Multidisciplinary cancer case presentation committee) patient's evaluation meeting
(either technically non-resectable metastases (absolute contraindication): i.e.
impossibility to resect all metastases in a single operation while preserving at
least 30% of healthy liver tissues and/or impossibility to preserve the portal vein
and hepatic artery homolateral to the liver or a portal pedicle, or due to
oncological non-resectability (relative contraindication): presence of > 5 nodules
and bilateral invasion),
- Hepatic metastases, without spread to other sites except in case of ≤ 3 resectable
pulmonary metastases of diameter < 2 cm, detected by thoracic scanner,
- K-Ras status determined before randomization,
- Measurable disease according to the RECIST V1.1 criteria,
- No prior treatment of the hepatic metastases,
- Previous 5FU +/- oxaliplatin-based adjuvant chemotherapy administered after
colorectal tumor resection is authorized if complete more than 1 year before,
- Age ≥ 18 & ≤ 75 years
- Performance status : ECOG 0 or 1,
- Life expectancy ≥ 3 months,
- Hemoglobin ≥ 9 g/dl,
- Polynuclear neutrophiles ≥ 1500/mm3,
- Platelets ≥ 100 000 mm3,
- Creatinemia ≤ 135 µmol/l (1,35 mg/dl)
- Total bilirubin ≤ 1.25 times the Upper Limit of Normal (ULN).
- Hepatic enzymes ASAT and ALAT < 5 x ULN,
- Negative pregnancy test for women of child-bearing age,
- Information given to the patient and signed informed consent,
- Public Health insurance coverage.
- Non metastatic and/or non measurable disease according to the RECIST v1.1 criteria.
- Non-resectable primary tumor (e.g.: T4 tumors) or incomplete resection R2.
- History of intestinal inflammatory disease.
- Specific contraindication to any of the study treatments.
- Patient who have previously received anti-EGFr (e.g., cetuximab) or anti-VEGF
monoclonal antibody treatment (e.g., bevacizumab) or treatment with irinotecan.
- History of cancer considered as not cured.
- Stroke/CVA or pulmonary embolism within 6 months before inclusion.
- Significant concomitant disease such as: coagulopathy, respiratory or cardiac
congestive insufficiency, non-medically controlled/unstable angina pectoris,
myocardial infarction within 6 months prior to study entry, arterial hypertension and
uncontrolled arrhythmia, severe infections.
- Clinical neuropathy, grade ≥1.
- Patient already included in another therapeutic trial using an experimental molecule.
- Pregnant women or women who might become pregnant during the study or lactating
- Men or women who can procreate and who do not abide with the use of a contraceptive
- Persons kept in detention or incapable of giving consent
- Patient unwilling or unable to comply with the medical follow-up required by the
trial because of geographic social or psychological reasons.